rs768983518

Variant names:

• chr13-45337499-A-G
• rs768983518
• NM_003295.4:c.517-111T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001286272.2(TPT1):​c.571T>C​(p.Leu191Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000506 in 1,461,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: TPT1 NM_001286272.2 synonymous
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 4.50
• Publications: 2 publications found

Genes affected

TPT1 (HGNC:12022): (tumor protein, translationally-controlled 1) This gene encodes a protein that is a regulator of cellular growth and proliferation. Its mRNA is highly structured and contains an oligopyrimidine tract (5'-TOP) in its 5' untranslated region that functions to repress its translation under quiescent conditions. The encoded protein is involved in a variety of cellular pathways, including apoptosis, protein synthesis and cell division. It binds to and stabilizes microtubules, and removal of this protein through phosphorylation is required for progression through mitotic and meiotic cell divisions. This gene is known to play a role in carcinogenesis, and is upregulated in some cancer cells. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2017]

SNORA31 (HGNC:32621): (small nucleolar RNA, H/ACA box 31)

SNORA31 Gene-Disease associations (from GenCC):

• encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 10

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia

ENSG00000273149 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.086).
• BS2: High AC in GnomAdExome4 at 74 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286272.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPT1	NM_003295.4	MANE Select	c.517-111T>C		intron	N/A	NP_003286.1	P13693-1
	TPT1	NM_001286272.2		c.571T>C	p.Leu191Leu	synonymous	Exon 6 of 6	NP_001273201.1	A0A0B4J2C3
	TPT1	NM_001286273.2		c.415-111T>C		intron	N/A	NP_001273202.1	P13693-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPT1	ENST00000530705.6	TSL:1 MANE Select	c.517-111T>C		intron	N/A	ENSP00000431872.2	P13693-1
	TPT1	ENST00000379056.5	TSL:1	c.415-111T>C		intron	N/A	ENSP00000368345.1	P13693-2
	TPT1	ENST00000616577.4	TSL:3	c.571T>C	p.Leu191Leu	synonymous	Exon 6 of 6	ENSP00000477781.1	A0A0B4J2C3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000521 AC: 13 AN: 249708 AF XY: 0.0000369

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000442

Gnomad OTH exome AF: 0.000329

GnomAD4 exome AF: 0.0000506 AC: 74 AN: 1461720 Hom.: 0 Cov.: 31 AF XY: 0.0000399 AC XY: 29 AN XY: 727168

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000157 AC: 7 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000576 AC: 64 AN: 1112006

Other (OTH) AF: 0.0000331 AC: 2 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.0000302

ClinVar

ClinVar submissions

Significance: risk factor

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 10 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Benign	0.90
PhyloP100		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs768983518; hg19: chr13-45911634;